Abstract P3-01-04: A real-world evidence study of everolimus plus endocrine therapy beyond CDK4/6 inhibitors for HR+/HER2- advanced breast cancer
Authors: Rodrigo Sánchez-Bayona, Manuel Alva, Alfonso López de sa, Yolanda Jerez Gilarranz, Ana Sánchez de torre, Pablo Tolosa, Alicia de luna, Sara López-Tarruella, Laura Lema, Fernando Moreno, Isabel Echavarria, Ainhoa Madariaga, Javier Benítez, Blanca Herrero, Macarena Rey, Justo Ortega, Salvador Gámez, Andrea Modrego, Rocío Martín Lozano, Luis Figuero-Pérez, Roberto Jiménez, Marta González Sevilla, Irene González, Marianela Bringas Beranek, María de toro, Tatiana Massarrah, María del Monte-Millán, Marina Pinardo, Luis Manso, Coralia Bueno-Muiño, José Ángel García-Sáenz, Miguel Martín, Eva Ciruelos
Journal: Cancer Research (2023)

Abstract Introduction Since the approval a decade ago of everolimus in combination with endocrine therapy (ET), the treatment landscape of metastatic breast cancer (mBC) has changed dramatically. Endocrine monotherapy after progression to CDK4/6 inhibitors has shown a limited progression-free survival (PFS) below 3 months. Evidence of the efficacy of everolimus plus ET after CDK4/6 inhibitors is scarce. Methods We performed a retrospective observational study of patients with mBC treated with everolimus between September 2011 and April 2022 in 4 Spanish hospitals. Clinical and demographic data were collected from medical records. Our main objective was to estimate the median progression-free survival (mPFS) for everolimus + ET in patients previously treated with a CDK4/6 inhibitor. We also collected the adverse events (AE) related to everolimus. Quantitative variables were summarized with medians (range), and qualitative variables with proportions. We used the Kaplan-Meier method for survival estimates. Results We identified a total of 297 mBC patients treated with everolimus plus ET. The median follow-up time was 20 months (interquartile range: 1 – 97 months). In this cohort, the median age at diagnosis was 49 years (26 – 84 years). At the moment of starting everolimus, the median number of previous lines of treatment was 2 (0 – 12), 22% of patients were ‘de novo’ metastatic, 67% presented visceral involvement, 40% had received previous chemotherapy for advanced disease, and 51% (n=152) had received a previous CDK4/6 inhibitor. The ET combined with everolimus was exemestane (77%), fulvestrant (18%), and tamoxifen (5%). 45% of patients were alive at data cut-off. In patients previously treated with a CDK4/6 inhibitor, the estimated median PFS (mPFS) was 5.9 months (95%CI: 5.0 – 7.8 months). In patients without visceral involvement (n=52), mPFS was 7.2 months (95%CI: 5.5 – 11.0 months), and 5.6 months (95%CI: 3.9 – 7.8 months) in the presence of visceral metastasis (n=100). In patients without previous chemotherapy in the metastatic setting (n=109), mPFS was 7.2 months (95%CI: 5.9 – 8.4 months), and 4.6 months (95%CI: 3.1 – 5.7 months) for patients who had received previous chemotherapy (n=43). For patients without a previous CDK4/6 inhibitor (n=145), the median PFS was 8.3 months (95%CI: 6.4 – 10.3 months). Everolimus starting doses were 10 mg (83%), 5 mg (15%), and 7.5 mg (2%). Dexamethasone mouthwash was used by 44% of patients. The most frequent AE were mucositis (51%; 3% grade 3), anemia (41%; 3% grade 3), hyperglycemia (34%; 2% grade 3), rash (28%; 2% grade 3), neumonitis (21%; 2% grade 3), and diarrhea (17%; 1% grade 3). There were no grade 4-5 adverse events. Dose reduction was made in 35% of patients, and in 16% of patients the treatment was discontinued due to toxicity. Conclusions In our cohort, the use of everolimus plus ET in mBC patients previously treated with a CDK4/6 inhibitor showed a clinically significant benefit in terms of PFS, especially in patients without visceral metastasis, and no previous chemotherapy for advanced disease. In this real-world study, the toxicity profile of everolimus was manageable. Citation Format: Rodrigo Sánchez-Bayona, Manuel Alva, Alfonso López de sa, Yolanda Jerez Gilarranz, Ana Sánchez de torre, Pablo Tolosa, Alicia de luna, Sara López-Tarruella, Laura Lema, Fernando Moreno, Isabel Echavarria, Ainhoa Madariaga, Javier Benítez, Blanca Herrero, Macarena Rey, Justo Ortega, Salvador Gámez, Andrea Modrego, Rocío Martín Lozano, Luis Figuero-Pérez, Roberto Jiménez, Marta González Sevilla, Irene González, Marianela Bringas Beranek, María de toro, Tatiana Massarrah, María del Monte-Millán, Marina Pinardo, Luis Manso, Coralia Bueno-Muiño, José Ángel García-Sáenz, Miguel Martín, Eva Ciruelos. A real-world evidence study of everolimus plus endocrine therapy beyond CDK4/6 inhibitors for HR+/HER2- advanced breast cancer. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-01-04.